Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia

Ryu Okumura, Takashi Kurakawa, Takashi Nakano, Hisako Kayama, Makoto Kinoshita, Daisuke Motooka, Kazuyoshi Goto, Taishi Kimura, Naganori Kamiyama, Takashi Kusu, Yoshiyasu Ueda, Hong Wu, Hideki Iijima, Soumik Barman, Hideki Osawa, Hiroshi Matsuno, Junichi Nishimura, Yusuke Ohba, Shota Nakamura, Tetsuya Iida & 4 others Masahiro Yamamoto, Eiji Umemoto, Koichi Sano, Kiyoshi Takeda

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified7-11. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8-/- mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8-/- mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.

Original languageEnglish
Pages (from-to)117-121
Number of pages5
JournalNature
Volume532
Issue number7597
DOIs
Publication statusPublished - Apr 7 2016

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Microbiota
Mucus
Epithelium
Bacteria
Dextran Sulfate
Epithelial Cells
Homeostasis
Paneth Cells
Inflammation
Proteus mirabilis
Architectural Accessibility
Flagella
Large Intestine
Intestinal Mucosa
Gram-Negative Bacteria
Small Intestine
Colon
Maintenance
Anti-Bacterial Agents
Peptides

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Okumura, R., Kurakawa, T., Nakano, T., Kayama, H., Kinoshita, M., Motooka, D., ... Takeda, K. (2016). Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature, 532(7597), 117-121. https://doi.org/10.1038/nature17406

Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. / Okumura, Ryu; Kurakawa, Takashi; Nakano, Takashi; Kayama, Hisako; Kinoshita, Makoto; Motooka, Daisuke; Goto, Kazuyoshi; Kimura, Taishi; Kamiyama, Naganori; Kusu, Takashi; Ueda, Yoshiyasu; Wu, Hong; Iijima, Hideki; Barman, Soumik; Osawa, Hideki; Matsuno, Hiroshi; Nishimura, Junichi; Ohba, Yusuke; Nakamura, Shota; Iida, Tetsuya; Yamamoto, Masahiro; Umemoto, Eiji; Sano, Koichi; Takeda, Kiyoshi.

In: Nature, Vol. 532, No. 7597, 07.04.2016, p. 117-121.

Research output: Contribution to journalArticle

Okumura, R, Kurakawa, T, Nakano, T, Kayama, H, Kinoshita, M, Motooka, D, Goto, K, Kimura, T, Kamiyama, N, Kusu, T, Ueda, Y, Wu, H, Iijima, H, Barman, S, Osawa, H, Matsuno, H, Nishimura, J, Ohba, Y, Nakamura, S, Iida, T, Yamamoto, M, Umemoto, E, Sano, K & Takeda, K 2016, 'Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia', Nature, vol. 532, no. 7597, pp. 117-121. https://doi.org/10.1038/nature17406
Okumura R, Kurakawa T, Nakano T, Kayama H, Kinoshita M, Motooka D et al. Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature. 2016 Apr 7;532(7597):117-121. https://doi.org/10.1038/nature17406
Okumura, Ryu ; Kurakawa, Takashi ; Nakano, Takashi ; Kayama, Hisako ; Kinoshita, Makoto ; Motooka, Daisuke ; Goto, Kazuyoshi ; Kimura, Taishi ; Kamiyama, Naganori ; Kusu, Takashi ; Ueda, Yoshiyasu ; Wu, Hong ; Iijima, Hideki ; Barman, Soumik ; Osawa, Hideki ; Matsuno, Hiroshi ; Nishimura, Junichi ; Ohba, Yusuke ; Nakamura, Shota ; Iida, Tetsuya ; Yamamoto, Masahiro ; Umemoto, Eiji ; Sano, Koichi ; Takeda, Kiyoshi. / Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. In: Nature. 2016 ; Vol. 532, No. 7597. pp. 117-121.
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